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Title: Enhancement of Paclitaxel-Induced Inhibition of Breast Cancer Cells by COL-3
Authors: Roba Marwan Hashiem El-Tabba’ 
Supervisor: Dr. Willias Masocha
Keywords: Paclitaxel-Induced Inhibition , Breast Cancer Cells, COL-3
Issue Date: 2016
Publisher:  Kuwait university - college of graduate studies
Abstract: The dose-dependent paclitaxel-induced neuropathic pain (PINP) hampers the use of paclitaxel as chemotherapeutic agent in the treatment of breast cancer and other solid tumors.Recently, chemically modified tetracycline-3 (COL-3 or CMT-3), a matrix metalloprotease (MMP) inhibitor, was reported to inhibit neuroinflammation, protect against PINP in micemodels and has anticancer activities. The aim of this study was to evaluate the effect of COL-3 on the anticancer activity of paclitaxel on different breast cancer cell lines; HBL-100, MCF-7 (estrogen receptor positive, ER+), pII (ER-) and MDA-MB-231 (ER-). Treatment with paclitaxel or COL-3 alone inhibited cell proliferation in a concentration-dependent manner in allfourcell lines. The anti-proliferative effects of paclitaxel and COL-3 in combination varied from synergism against MDA-MB-231 and pII cells tonearly additive andslight antagonism against HBL-100 and MCF-7 cells. In the highly proliferative and invasive pII cells,the observed synergisticanti-proliferative effect was shown to be in part through the induction of apoptosis, but not cell cycle arrest, and possiblythrough modulation of specific kinases and apoptosis-related proteins such as p53, p70S6 kinase, eNOS, EGFR and Hsp27. COL-3 inhibited invasion of pII cells in a concentration-dependent manner. The combination regimen significantly inhibited the expression of two proteases, ADAMTS1 and proteinase 3, and showed a trend towards inhibition of other proteases. In conclusion, the combination of paclitaxel and COL-3 exhibits additive to synergisticanti-proliferativeeffects on breast cancer cells mediated in part via induction of apoptosis and modulation of specific targets. The combination regimen could further inhibit invasion and metastasis. Thus, this suggests that COL-3 could be a useful adjunct to a paclitaxel-based anticancer regimen to improve both therapeutic outcome and reduce the adverse effects of paclitaxel mainly PINP.
Appears in Programs:2050 Molecular Biology

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